OBJECTIVES: The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). BACKGROUND: Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet aggregation; however, they differ mechanistically because aspirin acts via cyclooxygenase (COX) inhibition, while clopidogrel noncompetitively antagonizes the P2Y12 adenosine diphosphate receptor. We hypothesized that aspirin, due to its anti-inflammatory effects through inhibition of COX activity could inhibit arteriogenesis. Given that clopidogrel does not affect COX activity, it would be less likely to interfere with collateral artery growth. METHODS: Fifty-four New Zealand White rabbits received either saline, aspirin (10 mg/kg), or clopidogrel (10 mg/kg) for seven days after femoral artery ligation. Maximal collateral conductance was assessed with fluorescent microspheres under maximal vasodilation; cellular migration and proliferation (Ki-67) was evaluated by quantitative immunohistology. RESULTS: Collateral conductance was significantly reduced by aspirin treatment, whereas clopidogrel had a neutral effect (saline: 0.94 +/- 0.04; clopidogrel: 0.94 +/- 0.05; aspirin: 0.64 +/- 0.03 ml x min(-1) x 100 mm Hg(-1) x g(-1); p < 0.001). Ki-67 proliferation indexes were consistent with these results (saline: 23.1 +/- 2.9%; clopidogrel: 23.5 +/- 1.1%; aspirin: 19.2 +/- 1.1% Ki-67-positive cells). Immunohistochemistry showed COX expression in collateral arteries and a significantly decreased monocyte/macrophage accumulation in the perivascular tissue after aspirin treatment. Cell adhesion molecule expression on monocytes after activation was significantly reduced by aspirin, which might explain the reduced migratory ability. CONCLUSIONS: In summary, clopidogrel had a neutral effect on natural arteriogenesis. Aspirin significantly inhibited collateral artery growth, probably due to its anti-inflammatory effect. Additional studies are needed to substantiate these results before translation into clinical practice.
OBJECTIVES: The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). BACKGROUND:Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet aggregation; however, they differ mechanistically because aspirin acts via cyclooxygenase (COX) inhibition, while clopidogrel noncompetitively antagonizes the P2Y12 adenosine diphosphate receptor. We hypothesized that aspirin, due to its anti-inflammatory effects through inhibition of COX activity could inhibit arteriogenesis. Given that clopidogrel does not affect COX activity, it would be less likely to interfere with collateral artery growth. METHODS: Fifty-four New Zealand White rabbits received either saline, aspirin (10 mg/kg), or clopidogrel (10 mg/kg) for seven days after femoral artery ligation. Maximal collateral conductance was assessed with fluorescent microspheres under maximal vasodilation; cellular migration and proliferation (Ki-67) was evaluated by quantitative immunohistology. RESULTS: Collateral conductance was significantly reduced by aspirin treatment, whereas clopidogrel had a neutral effect (saline: 0.94 +/- 0.04; clopidogrel: 0.94 +/- 0.05; aspirin: 0.64 +/- 0.03 ml x min(-1) x 100 mm Hg(-1) x g(-1); p < 0.001). Ki-67 proliferation indexes were consistent with these results (saline: 23.1 +/- 2.9%; clopidogrel: 23.5 +/- 1.1%; aspirin: 19.2 +/- 1.1% Ki-67-positive cells). Immunohistochemistry showed COX expression in collateral arteries and a significantly decreased monocyte/macrophage accumulation in the perivascular tissue after aspirin treatment. Cell adhesion molecule expression on monocytes after activation was significantly reduced by aspirin, which might explain the reduced migratory ability. CONCLUSIONS: In summary, clopidogrel had a neutral effect on natural arteriogenesis. Aspirin significantly inhibited collateral artery growth, probably due to its anti-inflammatory effect. Additional studies are needed to substantiate these results before translation into clinical practice.
Authors: Nora Gatzke; Philipp Hillmeister; André Dülsner; Nadija Güc; Rica Dawid; Katherine H Smith; Nikolaos Pagonas; Peter Bramlage; Michaela Gorath; Ivo R Buschmann Journal: PLoS One Date: 2018-08-17 Impact factor: 3.240
Authors: Elisabeth Singer; Stephan Imfeld; Daniel Staub; Ulrich Hoffmann; Ivo Buschmann; Karl-Heinz Labs; Kurt A Jaeger Journal: J Am Heart Assoc Date: 2012-02-20 Impact factor: 5.501